Document Detail


The HTR3A polymorphism c. -42C>T is associated with amygdala responsiveness in patients with irritable bowel syndrome.
MedLine Citation:
PMID:  21420406     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: 5-Hydroxytryptamine (5-HT)3 receptor (5-HT3R) antagonists are effective in treating patients with irritable bowel syndrome (IBS) and have anxiolytic effects. Their therapeutic effects are related, in part, to reducing amygdala engagement during expected visceral pain. A single nucleotide polymorphism in HTR3A, c.-42C>T;(C178T; rs1062613), is associated with altered reactivity of the amygdala during emotional face processing in healthy subjects (controls). We evaluated the influence of this single nucleotide polymorphism on amygdala reactivity to emotional faces and nonemotional stimuli in female patients with IBS and controls.
METHODS: We measured brain responses during an affect-matching paradigm in 54 women (26 with IBS, 29 controls) using functional magnetic resonance imaging. We examined associations between HTR3A c.-42C>T genotype (C/C vs T carrier) and responses in amygdala and other regions of brain that expressed high levels of 5-HT3R.
RESULTS: The C/C genotype was associated with greater anxiety symptoms in patients with IBS and controls and increased activation of the amygdala under emotional and nonemotional conditions. Among patients with IBS, C/C genotype was associated with greater symptom ratings. A subset of IBS patients with the C/C genotype had increased amygdala responses to nonemotional stimuli, compared with other subjects with C/C genotype.
CONCLUSIONS: Regardless of diagnosis, the C/C genotype of the c.-42C>T polymorphism in HTR3A, compared with T carrier status, is associated with increased anxiety and amygdala responsiveness during emotional and nonemotional tasks. This polymorphism was associated with severity of IBS symptoms. Although this genotype is not sufficient for diagnosis of IBS, it is associated with severity of symptoms.
Authors:
Lisa A Kilpatrick; Jennifer S Labus; Kristen Coveleskie; Christian Hammer; Gudrun Rappold; Kirsten Tillisch; Joshua A Bueller; Brandall Suyenobu; Johana M Jarcho; Jim A McRoberts; Beate Niesler; Emeran A Mayer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-03-21
Journal Detail:
Title:  Gastroenterology     Volume:  140     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-06-06     Completed Date:  2011-08-09     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1943-51     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
Affiliation:
Center for Neurobiology of Stress, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California 90095, USA. lisa@lisakilpatrick.com
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MeSH Terms
Descriptor/Qualifier:
Adult
Amygdala / metabolism,  physiopathology*
Anxiety / genetics,  physiopathology
Brain Mapping / methods
Case-Control Studies
Emotions*
Facial Expression*
Female
Genetic Predisposition to Disease
Humans
Irritable Bowel Syndrome / diagnosis,  genetics*,  metabolism,  physiopathology
Los Angeles
Magnetic Resonance Imaging
Neuropsychological Tests
Phenotype
Polymorphism, Single Nucleotide*
Receptors, Serotonin, 5-HT3 / genetics*,  metabolism
Severity of Illness Index
Grant Support
ID/Acronym/Agency:
AT 002681/AT/NCCAM NIH HHS; DK 48351/DK/NIDDK NIH HHS; DK 64539/DK/NIDDK NIH HHS; P50 DK064539-01/DK/NIDDK NIH HHS; R01 DK048351-04/DK/NIDDK NIH HHS; R01 DK048351-14/DK/NIDDK NIH HHS; R24 AT002681-01/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
0/HTR3A protein, human; 0/Receptors, Serotonin, 5-HT3
Comments/Corrections

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